One or more cytotoxic and antineoplastic drugs are systemically used in chemotherapy treatment for cancer treatment. Today there is a wide variety of chemotherapeutic drugs used in treatment of various cancers. Paclitaxel, doxonibicin and cisplatin are some of the most known of these drugs. Although they have many side effects, antineoplastic effects thereof are determined in many studies. The chemotherapeutic drugs, which are cited in the literature and are used, do not exhibit full effect and additionally have a considerable number of side effects. Particularly cells which divide rapidly such as hair follicle or intestinal mucosa cells are affected by chemotherapeutic drugs. Suppression of immune system and the gastrointestinal problems constitute the main side effects that are observed. Hair loss and infertility are determined as the other main problems that are encountered during cancer treatment (Bryday et al., 2007). Hence a demand has emerged to develop new alternative treatment methods and chemical agents, which will minimize or eradicate the side effects occurring in the said treatment. Development of suitable pharmaceutical formulations cannot be possible only by eliminating the side effects. In the studies conducted, it is determined that molecules, whose cytotoxicity is defined and proved in in vitro and in vivo conditions should be prepared in the form of highly soluble formulations which maintain their stability (Gelderblom et al., 2001). It is known that paclitaxel as a proved chemotherapeutic drug in the literature has problems of poor solubility and stability (Li et al., 1996).
Compounds, which are formed as a result of condensation of aldehydes and ketones with primary amines under suitable reaction conditions, and which include C═N in their structure, are defined as Schiff base. It was demonstrated with the previous studies that Schiff bases, which can be used as catalysts in oxidation and reduction reactions, have anti-fungal and anti-bacterial effects and can be used as anti-microbial agents. One of the most important targets of the pharmacological studies is to develop new molecular agents which have anti-tumoral activity. This encourages inorganic and organometallic chemistry to develop new metal-containing drugs that may be effective against cancer.
There are studies in the literature showing usage of different Schiff bases against cancer. Organotin, which is a Schiff base derivative, has been used against seven different tumor cell lines, namely A498, EVSA-T, H226, IGROV, M19 MEL, MCF7 and MDR, and successful results have been obtained (Tushar et al. 2009). In another study, it was shown by using a liver cell line (Hep-G2) that Schiff base derivatives stop DNA synthesis by specifically inhibiting topoisomerase II without showing any mutagenic activity. Similarly, in another study using MCF7 which is the breast cancer cell line, Schiff base derivative showed significant amount of cytotoxic activity when compared with doxorubicin. It was also determined on neuroblastoma (SH-SY5Y) cells that. Schiff complexes disturb redox balance and thereby cause breaks in DNA and exhibit cytotoxic activity. These complexes can carry the metal residing in its structure via the cell membrane by targeting mitochondria and nucleus and cause oxidative stress and thus apoptosis. It was determined that copper containing Schiff base complexes activate apoptotic pathways thereby showing anticancer activity. In the previous studies with human breast cancer (MDA-MB-13 leukemia (Jurkat T), human colon cancer cells (HCT116) and pancreatic cancer (BxPC3) cells, it has been demonstrated that Schiff base copper complexes serve as a proteasome inhibitor and lead cancer cell death by causing accumulation of apoptotic proteins such as Bax (Zhang et al., 2008; Padhye et al.; 2009). Schiff base complexes exerted selectively anticarcinogenic activity on chronic myelogenic leukemia K562 cells when compared to MCF-12A cells which is the healthy cell line. (Aboul-Fadl et al.; 2012). In another study conducted with L1210 murine leukemia cells, Schiff base derivative has been more effective than hydroxyurea which is used in treatment of melanoma, leukemia and ovarian cancer (Ren et al.; 2002). It was determined in the previous studies that Schiff bases cause caspase-3 dependent apoptose in MDR (Multi Drug Resistance) cells by increasing the ROS (reactive oxygen species) content (Basu et al., 2011). Different Schiff base derivatives that were synthesized have been tried on many cancer cells such as cervical cancer (HeLa), leukemia (HL-60), cervical cancer (Caov-3), colon cancer (HT-29) and lung cancer (MRC-5) due to their antineoplastic activities (Ravoof et al., 2007; Chan et al., 2008).
Pluronic block copolymers Which are also known as poloxamers can be used for drug, growth factor and gene transport. The polymers are comprised of hydrophilic polyethyleneoxide and hydrophobic polypropyleneoxide units. Different numbers of ethylene oxide and propylene oxide monomers enable to obtain different pluronics. Each plutonic copolymer has different, biological effects. Since they are capable of forming micelle in liquid solutions, they can easily transport the drugs into the cells.
Studies related to Schiff base have also been conducted in the studies of state of the art applications Dede, B., Karipcin, F., and Cengiz, M. (2009).
The United States patent document no. US20130065864 discloses a combination containing iridium and/or rhodium for use in cancer treatment.
The European patent document no. EP2407164A1 discloses an anti-cancer complex which contains Cu-II compound and which can be in the form of a complex with different components.
The United States patent document no. U.S. Pat. No. 7,390,832B2 discloses a copper-based complex for treating tumors.